title: Refined exercise testing can aid DNA-based diagnosis in muscle channelopathies.
abstract: OBJECTIVE
  To improve the accuracy of genotype prediction and guide genetic testing in patients with muscle channelopathies we applied and refined specialized electrophysiological exercise test parameters.
  
  
  METHODS
  We studied 56 genetically confirmed patients and 65 controls using needle electromyography, the long exercise test, and short exercise tests at room temperature, after cooling, and rewarming.
  
  
  RESULTS
  Concordant amplitude-and-area decrements were more reliable than amplitude-only measurements when interpreting patterns of change during the short exercise tests. Concordant amplitude-and-area pattern I and pattern II decrements of >20% were 100% specific for paramyotonia congenita and myotonia congenita, respectively. When decrements at room temperature and after cooling were <20%, a repeat short exercise test after rewarming was useful in patients with myotonia congenita. Area measurements and rewarming distinguished true temperature sensitivity from amplitude reduction due to cold-induced slowing of muscle fiber conduction. In patients with negative short exercise tests, symptomatic eye closure myotonia predicted sodium channel myotonia over myotonia congenita. Distinctive "tornado-shaped" neuromyotonia-like discharges may be seen in patients with paramyotonia congenita. In the long exercise test, area decrements from pre-exercise baseline were more sensitive than amplitude decrements-from-maximum-compound muscle action potential (CMAP) in patients with Andersen-Tawil syndrome. Possible ethnic differences in the normative data of the long exercise test argue for the use of appropriate ethnically-matched controls.
  
  
  CONCLUSIONS
  Concordant CMAP amplitude-and-area decrements of >20% allow more reliable interpretation of the short exercise tests and aid accurate DNA-based diagnosis. In patients with negative exercise tests, specific clinical features are helpful in differentiating sodium from chloride channel myotonia. A modified algorithm is suggested.
authors.affiliation: Medical Research Council Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, University College London, Institute of Neurology London, UK. veronic.tan@uclh.nhs.uk
authors.forename: S Veronica
authors.initials: SV
authors.lastname: Tan
authors.forename: Emma
authors.initials: E
authors.lastname: Matthews
authors.forename: Melissa
authors.initials: M
authors.lastname: Barber
authors.forename: James A
authors.initials: JA
authors.lastname: Burge
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Rajakulendran
authors.forename: Doreen
authors.initials: D
authors.lastname: Fialho
authors.forename: Richa
authors.initials: R
authors.lastname: Sud
authors.forename: Andrea
authors.initials: A
authors.lastname: Haworth
authors.forename: Martin
authors.initials: M
authors.lastname: Koltzenburg
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053447:Channelopathies / Q000175:diagnosis* / Q000235:genetics; D004576:Electromyography; D005080:Exercise Test; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000175:diagnosis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology*; D020967:Myotonic Disorders / Q000175:diagnosis* / Q000235:genetics